Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection

Abstract

A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 μm were prepared by ultra-sonication method, and incorporated into poly(lactic-co-glycolic acid)/poly(lactic acid) (PLGA/PLA) MSs using spray-drying technique. Cross-sectional observation and X-ray diffraction analysis showed that drug microcrystals were evenly embedded in the MSs, with a distinctive crystalline nature of TA. In vitro drug release from the novel MSs was markedly decelerated compared to those from the marketed crystalline suspension (Triam inj.®), or even 7.2 μm-sized TA crystals-loaded MSs. The novel system offered prolonged drug retention in rat joints, providing quantifiable TA remains over 28 days. Whereas, over 95% of IA TA was removed from joints within seven days, after injection of the marketed product. Systemic exposure of the steroidal compound was drastically decreased with the MSs, with <50% systemic exposure compared to that with the marketed product. The novel MS was physicochemically stable, with no changes in drug crystallinity and release profile over 12 months. Therefore, the TA microcrystals-loaded MS is expected to be beneficial in patients especially with osteoarthritis, with reduced IA dosing frequency.

Bioactive Ibuprofen-Loaded PLGA Coatings for Multifunctional Surface Modification of Medical Devices

“…Similar but reduced-in-size structural modifications were also observed after 4, 6 and 10 days of dynamic testing ( Figure 6 c–e). This behavior might indicate a substantial swelling of PLGA matrix after 2 days, followed by progressive swelling and local reorganization of polymeric chains [ 74 , 75 ], but also accompanied by incipient microstructural alterations (fine cracks were identified after the considered testing intervals). Microstructural modifications identified until the 10 th day of dynamic studies evidenced a slow and gradual alteration of PLGA/IBUP coatings, in compliance with previous results on mass loss and drug release.…”

High‐Dose Steroid Dissolving Microneedle for Relieving Atopic Dermatitis

“…According to previous studies, in the dispersion process of TA powder using the sonication, TA powder was dispersed in a small size without crystalline changes, and TA exhibits stability for more than 1 day in an aqueous solution at room temperature. [ 16 ] After sonication of TA suspension, backbone polymers, which provide mechanical strength to DMN, such as hyaluronic acid (HA) and polyvinylpyrrolidone (PVP), were mixed with highly concentrated TA. These polymers have extra function as a stabilizer to prevent sedimentation of TA in the suspension.…”

Enhanced Darkfield Optical Microscopy Opens New Nano-Scale Imaging Possibilities

“…Of course, the creation of the ENMs is only the first step, as introducing them into a functional role is most often the ultimate goal. The EDF illumination technique has been used extensively across all aspects of the ENM life cycle, including projects such as development of designed silver nanoparticles (AgNPs) for use in water purification [2], building microcrystal-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres specifically for use in extended drug retention in joints [3], and the design of organic photovoltaics. In the last example, Torreggiani and colleagues [4] demonstrate the efficacy of a bi-continuous composite of electron donor and electron acceptor materials in boosting power conversion efficiency.…”